[The place of amisulpride in the atypical neuroleptic class]

Amisulpride is a benzamide derivative which displays a pharmacological profile distinct from that of classical neuroleptics such as haloperidol. In vitro, amisulpride selectively binds to dopamine (DA) receptors and is devoid of any affinity for serotonergic, alpha-adrenergic, histaminergic or muscarinic receptors. It has high and equal affinities for human D2 and D3 receptors, without affinity for D1 and D4 receptors. In vivo, in rats, amisulpride preferentially blocked D2 and D3 receptors localized in limbic structures in comparison with receptors found in the striatum. In addition, amisulpride selectively blocked presynaptic DA receptors. Thus, amisulpride antagonized apomorphine-induced effects (yawning, hypomotility) related to presynaptic DA receptor stimulation at very low doses (ED50 = 0.3-1 mg/kg, ip) compared to those needed to inhibit hypermotility and gnawing (60-80 mg/kg, ip) which involve post-synaptic DA receptor stimulation. The high affinity of amisulpride for D2 and D3 receptors, and its high degree of limbic selectivity may explain the lack of catalepsy in rats and the low incidence of neurological side effects in clinical studies. The enhancement of DA function produced by its selective presynaptic receptor DA blockade may account for the clinical efficacy of amisulpride against negative symptoms of schizophrenia.